Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes.
Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes.
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DOI：
10.1093/cid/cix254
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发表时间：
2017-07-01
期刊：
影响因子：
--
通讯作者：
Meintjes G
中科院分区：
文献类型：
--
作者：
Janssen S;Schutz C;Ward A;Nemes E;Wilkinson KA;Scriven J;Huson MA;Aben N;Maartens G;Burton R;Wilkinson RJ;Grobusch MP;Van der Poll T;Meintjes G
因与人体免疫缺陷病毒有关的结核病住院的病人的死亡率仍然高得令人无法接受。在这些患者中，一半患有分枝杆菌血症。死亡与较高浓度的免疫激活和抗炎标志物以及对细菌抗原的体外先天性应答受损相关。诊断为人类免疫缺陷病毒（HIV）相关结核病的住院患者的病死率仍然很高，结核分枝杆菌血症很常见。我们的目的是确定与12周死亡率相关的先天免疫反应的性质。这项前瞻性队列研究在南非开普敦Khayelitsha医院进行。纳入了CD 4计数<350个细胞/微升的住院HIV感染结核病患者;所有患者均进行了结核病血培养。招募无活动性结核病的非卧床HIV感染患者作为对照。用大肠杆菌衍生的脂多糖、热灭活的肺炎链球菌和结核分枝杆菌刺激全血。使用考克斯比例风险模型评估炎症和脓毒症的生物标志物、细胞内（流式细胞术）和分泌的细胞因子（Luminex）与12周死亡率的相关性。其次，我们研究了这些免疫标记物与结核分枝杆菌血症的关系。纳入60例患者（中位CD 4计数53个细胞/µL（四分位距[IQR]，22-132）; 16例（27%）在中位12（IQR，0-24）天后死亡。31株（52%）为M.血培养上的肺结核死亡率与较高浓度的降钙素原、先天性免疫系统激活（%CD 16 + CD 14+单核细胞、白细胞介素6、肿瘤坏死因子-β和集落刺激因子3）和TNF-α标志物（白细胞介素1受体拮抗剂增加和单核细胞和中性粒细胞对细菌刺激的反应降低）相关。结核分枝杆菌血症与死亡率无关，也与脓毒症的生物标志物无关。与严重细菌性脓毒症中报道的相似，12周死亡率与先天免疫系统的更大的前和后改变相关。
Mortality remains unacceptably high in patients hospitalized with human immunodeficiency virus–associated tuberculosis. Among these patients, half had mycobacteremia. Death was associated with higher concentrations of immune activation and anti-inflammatory markers, and impaired ex vivo innate responses to bacterial antigens. Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population. This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalized HIV-infected tuberculosis patients with CD4 counts <350 cells/µL were included; tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without active tuberculosis were recruited as controls. Whole blood was stimulated with Escherichia coli derived lipopolysaccharide, heat-killed Streptococcus pneumoniae, and Mycobacterium tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex), were assessed for associations with 12-week mortality using Cox proportional hazard models. Second, we investigated associations of these immune markers with tuberculosis mycobacteremia. Sixty patients were included (median CD4 count 53 cells/µL (interquartile range [IQR], 22–132); 16 (27%) died after a median of 12 (IQR, 0–24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony-stimulating factor 3), and antiinflammatory markers (increased interleukin-1 receptor antagonist and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis. Twelve-week mortality was associated with greater pro- and antiinflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis.
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DOI：
10.1186/cc5055
发表时间：
2006
期刊：
Critical care (London, England)
影响因子：
--
作者：
Cavaillon JM;Adib-Conquy M
通讯作者：
Adib-Conquy M
影响因子：
5.5
作者：
Aguilar-Ruiz, Sergio R.;Torres-Aguilar, Honorio;Sanchez-Torres, Carmen
通讯作者：
Sanchez-Torres, Carmen
影响因子：
3.7
作者：
Nakiyingi L;Ssengooba W;Nakanjako D;Armstrong D;Holshouser M;Kirenga BJ;Shah M;Mayanja-Kizza H;Joloba ML;Ellner JJ;Dorman SE;Manabe YC
通讯作者：
Manabe YC
影响因子：
3.7
作者：
Jacob, Shevin T.;Pavlinac, Patricia B.;Scheld, W. Michael
通讯作者：
Scheld, W. Michael
影响因子：
3.7
作者：
Odone, Anna;Amadasi, Silvia;Houben, Rein M. G. J.
通讯作者：
Houben, Rein M. G. J.